Figure 6. A Gating model.

In the absence of Ca²⁺, hydrophobic block at the neck prevents ion flow (Ca²⁺-free closed). When the Ca²⁺ clasps are occupied by Ca²⁺, the channel is in equilibrium between Ca²⁺-bound closed and Ca²⁺-bound open conformations. The dramatic widening of the opened neck enables hydrated ions to flow through it. Binding of the inactivation peptide to its cytosolic receptor, which is stimulated by higher concentrations (>500 nM) of Ca²⁺, induces the Ca²⁺-bound inactivated conformation in which the neck is closed. The aperture, which remains fixed throughout the gating cycle, acts as a size-selective filter that requires permeating ions to become at least partially dehydrated as they pass though it, and this engenders the channel’s lyotropic permeability sequence.